SMOKELESS TOBACCO EFFECTS ON MONOCYTE SECRETION OF PGE(2) AND IL-1-BETA

THE USE OF SMOKELESS TOBACCO (ST) PRODUCTS is associated with mucosal lesions, gingival recession, and attachment loss at the site of tobacco placement. Monocytes/macrophages are primary producers of PGE(2) and IL-1 beta, inflammatory mediators which are thought to play a role in the destruction of the periodontium. The purpose of this study was to determine the effect of ST alone and in combination with a major stimulator of inflammation, bacterial lipopolysaccharide (LPS), on monocyte secretion of these mediators. Peripheral blood monocytes (PBM) were isolated by counterflow centrifugal elutriation from 15 healthy donors who were non-ST users. PBM were incubated for 24 hours in RPMI 1640 containing various concentrations of ST (0%, 0.005%, 0.01%, 1%) with or without 10 mu g/ml LPS (Porphyromonas gingivalis LPS or Escherichia coli LPS). Of the ST preparations, only 1% ST resulted in PBM mediator secretion (7.7 +/- 2.0 ng/ml for PGE(2) and 1.3 +/- 0.2 ng/ml for IL-1 beta) above that of control (unstimulated) cultures. Furthermore, the combination of 1% ST and LPS resulted in a potentiation of PGE(2) release (5-fold for E. coli LPS + 1% ST and 10-fold for P. gingivalis LPS + 1% ST; P < 0.0001, one-way ANOVA) relative to the LPS preparations alone. In contrast, PBM IL-1 beta release decreased more than 2-fold upon E. coli LPS and 1% ST exposure, relative to treatment with E. coli LPS alone (P < 0.0001, one-way ANOVA). PBM IL-1 beta release either increased or decreased following treatment with P. gingivalis LPS + 1% ST, depending on the magnitude of the P. gingivalis LPS response alone. These data indicate that ST has profound effects on monocyte secretion of PGE(2) and IL-1 beta, and modulates the LPS-mediated monocyte response.